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Qiyu Jia,1,* Lu Liu,1,* Yunyuan Yu,2,* Wuhuzi Wulamu,1 Lin Jia,1 Bo Liu,1 Hao Zheng,3 Zhenlei Peng,1 Xiaogang Zhang,1 Ruixia Zhu2 1The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Department of orthopedics, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 3The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruixia Zhu, Department of Orthopaedics, the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, 213003, People’s Republic of China, Email ZRX_1982@sina.com Xiaogang Zhang, The First Affiliated Hospital of Xinjiang Medical University, 137 Liyue Shan South Road, Xinshi District, Urumqi, 830054, People’s Republic of China, Email zxgjohn1972@sina.comPurpose: The polarization of macrophages towards the pro-inflammatory M1 phenotype and osteoclast overactivation play a significant role in the pathogenesis of aseptic loosening of orthopedic implants. This study sought to examine the expression and activation of macrophages and osteoclasts in implant biopsies with respect to epidermal growth factor receptor (EGFR) signaling and to assess the potential of EGFR inhibition in mitigating titanium particle-induced bone resorption in a cranial resorption murine model.Methods: Bone marrow-derived macrophages (BMDMs) were stimulated with Tumor Necrosis Factor-alpha (TNF-α) and Interferon-gamma (IFN-γ) initially. Subsequently, Osteoclast differentiation was initiated after Gefitinib was added to the treatment groups. Male C57BL/6 mice were treated with Gefitinib or 0.5% Carboxymethyl Cellulose-Sodium (CMC-Na) by oral gavage daily for two weeks. A sham group received no further intervention, while the other groups had titanium particles implanted. Tissues were collected and analyzed by measurements such as micro-computed tomography (micro-CT) analyses, histology, immunofluorescence stainings, cell viability assays, assays for resorption pit formation, Reverse Transcription-Polymerase Chain Reactions (RT-PCRs), and Western blots were conducted.Results: The study demonstrated a significant upregulation of EGFR in response to titanium particle exposure. Inhibition of EGFR phosphorylation with gefitinib effectively reduced bone degradation at osteolytic sites in a murine model. Gefitinib treatment led to a notable reduction in M1 macrophage polarization, as indicated by immunofluorescence staining and Western blot analysis of macrophage markers. Mechanistically, selective EGFR inhibitors mitigate osteoclastogenesis and osteoclast resorption by inhibiting the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor-κB (NF-κB) signaling pathways.Conclusion: Our findings provide compelling evidence of the essential role of EGFR-related pathways in M1 polarization, osteoclast activation, and ensuing periprosthetic osteolysis. Overall, EGFR presents a novel target for addressing bone resorption-associated conditions triggered by particles or modulated by macrophages and osteoclasts.Keywords: EGFR, Wear particles, osteoclast, bone resorption, macrophage polarization

Abstract Background Depression is a significant health concern among children and adolescents. Previous epidemiological studies on depressive symptoms in this population have yielded inconsistent findings. This study aims to systematically estimate the prevalence of depressive symptoms among Chinese children and adolescents. Method A comprehensive literature search was conducted in both English (PubMed, EMBASE) and Chinese (China National Knowledge Infrastructure, WANFANG) databases from their inception until October 15, 2024. This meta-analysis employed a random-effects model to estimate the pooled prevalence of depressive symptoms. Results A total of 439 eligible studies, comprising 1,497,524 participants, were included in the analysis. The pooled point prevalence of depressive symptoms among children and adolescents was found to be 26.17% (95% CI 25.00–27.41%), with significant heterogeneity among studies (I2 = 100%, p

Abstract Background Radiographically, ground-glass nodules (GGN) and part-solid nodules (PSN) in lung adenocarcinoma (LUAD) have significant heterogeneity in their clinical manifestations, biological characteristics, and prognosis. This study aimed to explore the heterogeneity of LUAD in different radiological phenotypes and associated factors influencing tumor evolution. Methods We performed single-cell RNA sequencing (scRNA-seq) on tumor tissues from eight and seven cases of GGN– and PSN–LUAD, respectively, at different disease stages, including minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IAC), and metastatic lung cancer (MLC). Additionally, we analyzed adjacent normal tissues from four cases. Immunohistochemistry, multiplex immunofluorescence, and external scRNA-seq data were employed to confirm the expression of signature genes as well as the distribution patterns of CXCL9 + TAMs and TREM2 + TAMs. A LUAD mouse model was generated using gene editing, organoid culture, and orthotopic transplantation techniques, and comprehensive analyses such as histopathology, RNA sequencing, and Western blotting were performed to validate key pathways. Results Diverse cellular compositions were observed in the tumor microenvironment (TME) during GGN– and PSN–LUAD invasion and metastasis. Notably, CXCL9 + and TREM2 + tumor-associated macrophages (TAMs) exhibited the most significant enrichment changes. It was found that GGN–LUAD exhibited a stronger immune response than PSN–LUAD, with increased interaction between CXCL9 + TAMs and CD8 + tissue-resident memory T cells during invasion stage (MIA–IAC). Conversely, greater interactions between TREM2 + TAMs and tumor cells were observed in PSN–LUAD during the MLC stage. Additionally, TREM2 + TAMs were found to differentiate into TREM2 + /SPP1 + and TREM2 + /SPP1– TAMs at different stages, which promotes tumor progression. This study also emphasizes that during the transdifferentiation process of GGN– and PSN–LUAD, IFN-γ activates the STAT1 signaling pathway to regulate the activation of CXCL9 + TAMs, and further recruiting CD8 + Trm cells and activating T cells through MHC class I antigen presentation. The role of the IFN-γ/STAT1 pathway in the occurrence and development of LUAD was further validated by animal experiments. Conclusions Our findings offer a potential therapeutic strategy to maintain a dynamic balance within the TME and improve the immunotherapy efficacy by modulating the relative proportions and functional states of CXCL9 + TAMs and TREM2 + TAMs.

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by an insidious onset. Despite the emphasis on motor symptom-based diagnosis, there remains an unmet clinical need for effective diagnostic approaches during the prodromal phase of PD. Recent advances in single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic analyses of PD patients open avenues for identifying potential diagnostic biomarkers. A comprehensive cell trajectory analysis was conducted using scRNA-seq datasets to identify gene expressions associated with the cellular transition from healthy to PD-associated states. Integration of scRNA-seq datasets with weighted gene co-expression network analysis (WGCNA) allowed extraction of pyroptosis-associated differentially expressed genes (PDEGs). Using LASSO logistic regression, support vector machine recursive feature elimination (SVM-RFE) and random forest methods, we developed a diagnostic model centred on PDEGs. In addition, immunoinfiltration, inflammatory signalling pathways and intercellular communication were detected by scRNA-seq analyses. In PD patients, the number of cells including metencephalic-like cells, excitatory neurons, inhibitory neurons and MHB-like cells was significantly reduced, whereas the proportion of astrocytes and microglia, immunoinfiltration and inflammatory signalling pathways were upregulated compared to healthy individuals. Using scRNA-seq and WGCNA analyses, two pyroptosis-related diagnostic genes, POLR2K and TIMM8B, were identified and a diagnostic model based on them was constructed, which showed promising performance upon validation. This study established a pyroptosis-related diagnostic model for PD through the analyses of scRNA-seq combined with bulk transcriptome data, which improved the understanding of the role of PDEGs in PD and provided new insights into the diagnostic strategies for this neurodegenerative disease.

Abstract Background Anaplastic thyroid carcinoma (ATC) is a rare but the most aggressive type of thyroid carcinoma. Nevertheless, limited advances were made to reduce mortality and improve survival over the last decades. Therefore, identifying novel diagnostic biomarkers and therapeutic targets for ATC patients is still needed. Materials and methods RNA sequencing data and corresponding clinical features were available from GEO and TCGA databases. We integrated WGCNA and PPI network analysis to identify hub genes associated with ATC development, and RT-qPCR was employed for data verification. Univariate and LASSO Cox regression analyses were used to generate prognostic signatures. Results Based on PPI and WGCNA, 6 hub genes were identified, namely KIF2C, PBK, TOP2A, CDK1, KIF20A, and ASPM, which play vital roles in ATC development. Subsequently, RT-qPCR experiments showed that most of these genes were significantly upregulated in CAL-62 cells compared to Nthy-ori 3–1 cells. Moreover, a prognostic signature featuring GPSM2, FGF5, ASXL3, CYP4B1, CLMP, and DUXAP9 was generated, which was also verified by RT-qPCR results and proved as an independent predictor of poorer prognosis of ATC. Additionally, a nomogram incorporating the risk score and clinicopathological parameters was further constructed for accurate prediction of 1-, 3- and 5-year survival probabilities of ATC. Conclusions Our study identified 6 key genes critical to ATC development and constructed a prognostic signature. These findings provide reliable biomarkers and a relatively comprehensive tumorigenesis profile of ATC, which may inform future strategies for clinical diagnosis and pharmaceutical design.

Abstract Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma, with poor prognosis and limited treatment options. The genomic features of ICC in Chinese patients remain largely unknown. In this study, we perform deep whole-exome sequencing of 204 Chinese primary ICCs and characterize genomic alterations and clonal evolution, and reveal their associations with patient outcomes. We identify six mutational signatures, including Signatures A and F, which are highly similar to previously described signatures linked to aristolochic acid and aflatoxin exposures, respectively. We also identify 13 significantly mutated genes in the ICC samples, including SAV1. We find that SAV1 was mutated in 2.9% (20/672) of 672 ICC samples. SAV1 mutation is associated with lower SAV1 protein levels, higher rates of tumor recurrence, and shorter overall patient survival. Biofunctional investigations reveal a tumor-suppressor role of SAV1: its inactivation suppresses Hippo signaling, leading to YAP activation, thereby promoting tumor growth and metastasis. Collectively, our results delineate the genomic landscape of Chinese ICCs and identify SAV1 as a potential driver of ICC.

Abstract Although the incidence of cervical cancer (CC) has been reduced in high-income countries due to human papillomavirus (HPV) vaccination and screening strategies, it remains a significant public health issue that poses a threat to women’s health in low-income countries. Here, we perform a comprehensive proteogenomic profiling of CC tumors obtained from 139 Chinese women. Integrated proteogenomic analysis links genetic aberrations to downstream pathogenesis-related pathways and reveals the landscape of HPV-associated multi-omic changes. EP300 is found to enhance the acetylation of FOSL2-K222, consequently accelerating the malignant proliferation of CC cells. Proteomic stratification identifies three patient subgroups with distinct features in prognosis, genetic alterations, immune infiltration, and post-translational modification regulations. PRKCB is further identified as a potential radioresponse-related biomarker of CC patients. This study provides a valuable public resource for researchers and clinicians to delve into the molecular basis of CC, to identify potential treatments and to ultimately advance clinical practice.

Abstract Background Previous studies have demonstrated that asthma is closely associated with bronchiectasis, however, the causal relationship between asthma and bronchiectasis has not been investigated in depth. Therefore, this study aims to explore the causal relationship and to identify potential factors that mediate between these two diseases. Method All the necessary summarized information were obtained from publicly available genome-wide association study (GWAS). Two-sample Mendelian randomization (two-sample MR) was employed to explore the causal relationship between asthma and bronchiectasis, with an additional dataset used for validation. Heterogeneity and pleiotropy analyses were utilized to verify the robustness of the results. Subsequently, mediation MR analyses were performed to identify potential mediating factors. Lastly, a retrospective observational study was conducted to validate the findings. Result Preliminary inverse-variance weighted (IVW) results indicated there was a causal effect of asthma on bronchiectasis (odds ratio [OR] = 1.228, 95% confidence interval [CI]: 1.077–1.400, P = 0.002). Repetition validation yielded a consistent result. Mediation MR analysis demonstrated that the presence of nasal polyps (OR = 1.063, 95% CI: 1.015–1.113, mediation ratio = 30.492%, P = 0.009), acute sinusitis (OR = 1.062, 95% CI: 1.009–1.118, mediation ratio = 30.157%, P = 0.018), chronic sinusitis (OR = 1.085, 95% CI: 1.024–1.150, mediation ratio = 40.677%, P = 0.005), and peripheral eosinophil counts (OR = 1.013, 95% CI: 1.000–1.026, mediation ratio = 6.514%, P = 0.042) served as significant mediators in the occurrence and development of bronchiectasis induced by asthma. Furthermore, a retrospective observational study observed that bronchiectasis patients with asthma had a higher prevalence of sinusitis (5.043% vs 2.971%, P

As a novel functional component, γ-aminobutyric acid (GABA) with many kinds of functions of regulating blood pressure, alleviating depression, treating epilepsy, delaying aging and treating diabetes, is widely distributed in a large variety of plants. It is reported that plant germination was recognized as an effective way to raise endogenous GABA levels, which in combination with several environmental stress modes could further promote GABA enrichment in germinating plants. This paper mainly discusses the metabolic pathways and influence factors of GABA enrichment in plants, as well as the synergistic effects of environmental stress and germination on endogenous GABA enrichment in plants, providing references for the development and application of GABA-rich plant-based foods.

Backgrounds/Aims Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Methods We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusions We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Objective To explore the inhibitory effect of berberine （BBR） on contrast-induced nephropathy （CIN） and clarify the underlying mechanism. Methods Sprague-Dawley （SD） rats were utilized for constructing a rat CIN model. BBR treatment group （M+B） received a gavage of 200 mg/kg BBR while control group （Con） and model group （Mod） had an oral intake of the same volume of normal saline. Human kidney cortex proximal tubule epithelial cells （HK-2） were utilized for constructing a CIN cell model in vitro. No special treatment was offered to HK-2 cells in Con group. HK-2 cells in Mod group were treated with 50 g/L ioversol for 24 h and HK-2 cells in M+B group 50 g/L ioversol and 30 μmol/L BBR for 24 h. Akt agonist （SC79） and Akt inhibitor （MK2206） were utilized for confirming the effect of BBR on protein kinase B-forkhead box O3-nuclear factor erythroid 2-related factor 2 （Akt-Foxo3a-Nrf2） regulatory axis. Serum creatinine （Scr） detection and hematoxylin-eosin （HE） stain were employed for evaluating renal injury in rats. Annexin V-propidium iodide （annexin V-PI） stain was used for detecting cell apoptosis. And Western blot was utilized for detecting the protein expression of Akt-Foxo3a-Nrf2 axis.Results The level of Scr was higher in Mod group than that in Con group [（58.83 ± 7.96）μmol/L vs （23.52 ± 0.78）μmol/L，P＜0.05]. And it was lower in M+B group than that in Mod group [（39.64 ± 2.52）μmol/L vs （58.83 ± 7.96）μmol/L，P＜0.05]. HE stain indicated that kidney morphology was normal and renal tubular epithelial cells remained intact in Con group. In Mod group， structure of renal tubules was disarrayed with diffuse death of epithelial cells and obvious vacuolar degeneration of renal tubular epithelial cells. In M+B group， morphology of renal tubules was partially restored and vacuolar degeneration of renal tubule epithelial cells and cell death lessened. Western blot results indicated that， as compared with Con group， the expression of phospho-protein kinase B （p-Akt） was up-regulated in CIN rats and ioversol treated HK-2 cells. And the difference was statistically significant （P＜0.05）. In M+B group， the expression of p-Akt dropped as compared with Mod group （P＜0.05）. Annexin V-PI apoptosis assay indicated that， as compared with Con group， cell apoptosis spiked in Mod group [（12.65 ± 1.25）% vs （27.44 ± 0.73）%，P＜0.05]. As compared with Mod group， cell apoptosis declined in M+B group [（27.44 ± 0.73）% vs （24.81 ± 0.49）%，P＜0.05]. As compared with M+B group， cell apoptosis rose in BBR plus SC79 treatment group [（24.81 ± 0.49）% vs （27.50 ± 0.35）%，P＜0.05]. As compared with Mod group， cell apoptosis declined in MK2206 treatment group [（27.65 ± 0.56）% vs （25.20 ± 0.64）%，P＜0.05]. As compared with M+B group， MK2206 plus BBR further reduced ioversol-induced HK-2 cell apoptosis [（24.51 ± 0.52）% vs （21.24 ± 0.99）%，P＜0.05]. Conclusion BBR may suppress CIN in vivo and in vitro through regulating Akt-Foxo3a-Nrf2 axis in a p-Akt dependent mode.

Abstract Background Traditional chemotherapeutic agents suffer from a lack of selectivity, poor targeting ability, and drug resistance. Developing tumor-specific therapies is crucial for precisely eliminating tumors while circumventing toxicity to normal tissues. Disulfiram (DSF), an FDA-approved drug for treating alcohol dependence, exhibits antitumor effect by forming complexes with copper ions (Cu(DDC)2). Here, we developed a Cu-doped polydopamine-based nanosystem (DSF@CuPDA-PEGM) to achieve in situ generation of toxic Cu(DDC)2. Results In cancer cells with elevated H2O2 contents, CuPDA responsively degrades to release Cu ions and DSF, allowing on-site synthesis of Cu(DDC)2 with potent antitumor activity. DSF@CuPDA-PEGM exhibits excellent therapeutic efficacy against both drug-sensitive and drug-resistant cancer cells while minimizing toxicity to noncancerous cells. Moreover, DSF@CuPDA-PEGM promotes the immune response by inducing cancer cell immunogenic death, thereby augmenting anti-PD-1-based immune checkpoint blockade therapy. Conclusion A tumor-specifically degradable Cu-doped polydopamine-based nanosystem is developed to achieve in situ synthesis of antitumor compounds, providing a promising approach to precisely eliminate tumors and heighten chemo-immunotherapy. Graphical Abstract

This study describes a new species, Sinocyclocheilus xiejiahuai sp. nov., discovered within a cave located in Hongguo Town, Panzhou City, Guizhou Province, southwestern China, with the type locality in the Nanpanjiang River basin. Phylogenetic trees reconstructed based on mitochondrial genes show that the new species represents an independent evolutionary lineage with large genetic differences, 1.9%–13.8% in mitochondrial Cyt b, from congeners. Morphologically, this species can be differentiated from the 79 species currently classified under the genus Sinocyclocheilus by several characteristics: absence of horn-like structures and indistinct elevation at the head-dorsal junction, absence of irregular black markings on the body lateral and scaleless, eyes large, eye diameter 13% of head length, dorsal-fin rays, iii, 6½, last unbranched ray strong, with serrations along posterior margin, pectoral-fin rays, i, 13, anal-fin rays, iii, 5, pelvic-fin rays, i, 7, lateral line pores 74, gill rakers well developed, nine on first gill arch, pectoral fins short, tip not reaching to pelvic-fin origin. The number of Sinocyclocheilus species has been increased from 79 to 80 since the description of this new species.

Abstract Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

AbstractThe main purpose of this study was to explore the changes of biomarkers in different developmental stages of bleomycin-induced pulmonary fibrosis (PF) in rats via comprehensive pathophysiology, UPLC-QTOF/MS metabonomic technology, and 16S rRNA gene sequencing of intestinal microbiota. The rats were randomly divided into normal control and 1-, 2- and 4-week model group. The rat model of PF was established by one-time intratracheal instillation of bleomycin. The levels of inflammatory and fibrosis-related factors such as hydroxyproline (HYP), type III procollagen (COL-III), type IV collagen (COL-IV), hyaluronidase (HA), laminin (LN), interleukin (IL)-1β, IL-6, malondialdehyde (MDA) increased and superoxide dismutase (SOD) decreased as the PF cycle progressed. In the 1-, 2- and 4-week model group, 2, 19 and 18 potential metabolic biomarkers and 3, 16 and 12 potential microbial biomarkers were detected, respectively, which were significantly correlated. Glycerophospholipid metabolism pathway was observed to be an important pathway affecting PF at 1, 2 and 4 weeks; arginine and proline metabolism pathways significantly affected PF at 2 weeks. Linoleic acid metabolism pathway exhibited clear metabolic abnormalities at 2 and 4 weeks of PF, and alpha-linolenic acid metabolism pathway significantly affected PF at 4 weeks.

AbstractAlthough the gut microbial metabolites exhibit potential effects on coronary heart disease (CHD), the underlying mechanism remains unclear. In this study, the active gut microbial metabolites acting on CHD and their potential mechanisms of action were explored through a network pharmacological approach. We collected a total of 208 metabolites from the gutMgene database and 726 overlapping targets from the similarity ensemble approach (SEA) and SwissTargetPrediction (STP) database, and ultimately identified 610 targets relevant to CHD. In conjunction with the gutMGene database, we identified 12 key targets. The targets of exogenous substances were removed, and 10 core targets involved in CHD were eventually retained. The microbiota–metabolites–targets–signalling pathways network analysis revealed that C-type lectin receptor signalling pathway, Lachnospiraceae, Escherichia, mitogen-activated protein kinase 1, prostaglandin-endoperoxidase synthase 2, phenylacetylglutamine and alcoholic acid are notable components of CHD and play important roles in the development of CHD. The results of molecular docking experiments demonstrated that AKT1-glycocholic acid and PTGS2-phenylacetylglutamine complexes may act on C-type lectin receptor signalling pathways. In this study, the key substances and potential mechanisms of gut microbial metabolites were analysed via network pharmacological methods, and a scientific basis and comprehensive idea were provided for the effects of gut microbial metabolites on CHD.

Abstract Using 7.33 fb −1 of e + e − collision data samples collected with the BESIII detector at center-of-mass energies between 4.128 and 4.226 GeV, we search for the radiative decay D s + → γρ 770 + $$ {D}_s^{+}\to \gamma \rho {(770)}^{+} $$ for the first time. A hint of D s + → γρ 770 + $$ {D}_s^{+}\to \gamma \rho {(770)}^{+} $$ is observed with a statistical significance of 2.5σ. The branching fraction of D s + → γρ 770 + $$ {D}_s^{+}\to \gamma \rho {(770)}^{+} $$ is measured to be (2.2 ± 0.9stat. ± 0.2syst. ) × 10 −4, corresponding to an upper limit of 6.1 × 10 −4 at the 90% confidence level.

Abstract A complete goat (Capra hircus) reference genome enhances analyses of genetic variation, thus providing insights into domestication and selection in goats and related species. Here, we assemble a telomere-to-telomere (T2T) gap-free genome (2.86 Gb) from a cashmere goat (T2T-goat1.0), including a Y chromosome of 20.96 Mb. With a base accuracy of >99.999%, T2T-goat1.0 corrects numerous genome-wide structural and base errors in previous assemblies and adds 288.5 Mb of previously unresolved regions and 446 newly assembled genes to the reference genome. We sequence the genomes of five representative goat breeds for PacBio reads, and use T2T-goat1.0 as a reference to identify a total of 63,417 structural variations (SVs) with up to 4711 (7.42%) in the previously unresolved regions. T2T-goat1.0 was applied in population analyses of global wild and domestic goats, which revealed 32,419 SVs and 25,397,794 SNPs, including 870 SVs and 545,026 SNPs in the previously unresolved regions. Also, our analyses reveal a set of selective variants and genes associated with domestication (e.g., NKG2D and ABCC4) and cashmere traits (e.g., ABCC4 and ASIP).

Abstract The capacity to discern and locate positions in three-dimensional space is crucial for human-machine interfaces and robotic perception. However, current soft electronics can only obtain two-dimensional spatial locations through physical contact. In this study, we report a non-contact position targeting concept enabled by transparent and thin soft electronic skin (E-skin) with three-dimensional sensing capabilities. Inspired by the active electrosensation of mormyroidea fish, this E-skin actively ascertains the 3D positions of targeted objects in a contactless manner and can wirelessly convey the corresponding positions to other devices in real-time. Consequently, this E-skin readily enables interaction with machines, i.e., manipulating virtual objects, controlling robotic arms, and drones in either virtual or actual 3D space. Additionally, it can be integrated with robots to provide them with 3D situational awareness for perceiving their surroundings, avoiding obstacles, or tracking targets.

Abstract Using e + e − collision data collected by the BESIII detector at BEPCII corresponding to an integrated luminosity of 30 fb −1, we measure Born cross sections and effective form factors for the process e + e − → Ξ 0 Ξ ¯ 0 $$ {e}^{+}{e}^{-}\to {\Xi}^0{\overline{\Xi}}^0 $$ at forty-five center-of-mass energies between 3.51 and 4.95 GeV. The dressed cross section is fitted, assuming a power-law function plus a charmonium(-like) state, i.e., ψ(3770), ψ(4040), ψ(4160), ψ(4230), ψ(4360), ψ(4415) or ψ(4660). No significant charmonium(-like) state decaying into Ξ 0 Ξ ¯ 0 $$ {\Xi}^0{\overline{\Xi}}^0 $$ is observed. Upper limits at the 90% confidence level on the product of the branching fraction and the electronic partial width are provided for each decay. In addition, ratios of the Born cross sections and the effective form factors for e + e − → Ξ 0 Ξ ¯ 0 $$ {e}^{+}{e}^{-}\to {\Xi}^0{\overline{\Xi}}^0 $$ and e + e − → Ξ − Ξ ¯ + $$ {e}^{+}{e}^{-}\to {\Xi}^{-}{\overline{\Xi}}^{+} $$ are also presented to test isospin symmetry and the vector meson dominance model.

Abstract Objective The study was to survey the current situation and explore the relationship between pain assessment ability, palliative care core competence and palliative care practice ability among oncology nurses in mainland China. Methods A multicenter cross-sectional study design was employed. Study data were collected in 26 tertiary hospitals among 1198 registered oncology nurses in the oncology department in Hubei province, China. A web-based survey was conducted using a stratified random integral sampling method to obtain data. All variables were measured using standardized instruments. Data was analyzed using SPSS 26.0 and AMOS 26.0 statistical software. All statistical tests were two-sided, with the significance level set at P

Abstract Object detection in drone aerial images is challenging due to the difficulty of small object detection and complex backgrounds. To address these issues, this paper proposes an improved object detection model, perception and target capture detector (PTCDet), to increase detection accuracy and robustness in complex scenes. Specifically, the proposed multiple feature extraction attention (MFEA) module significantly enhances the ability of the model to detect small objects through multidimensional feature map augmentation. The weighted perceptive field augmentation (WPFA) module is designed to improve the contextual awareness and feature representation of the model, optimizing detection accuracy for small objects. Based on the multiscale feature fusion structure, an enhanced scale fusion detection (ESFD) module is used to improve small object detection by generating larger scale feature maps. Ultimately, the inner focaler IoU loss (INFL) function effectively accelerates the regression of detection bounding boxes, enhancing the generalization ability and overall detection performance of the model. The experimental results on three public datasets demonstrate that PTCDet outperforms other detection algorithms. For example, on the VisDrone dataset, compared with the baseline model YOLOv8, map@0.5 and map@0.5:0.95 are improved by 6.21% and 4.21%, respectively. PTCDet exhibits excellent performance in addressing complex backgrounds and small object detection, providing an effective and robust solution for object detection tasks in drone aerial images.

Abstract Changes in diet causing ecological stress pose a significant challenge to animal survival. In response, the gut microbiota, a crucial part of the host’s digestive system, exhibits patterns of change reflective of alterations in the host’s food component. The impact of temporal dietary shifts on gut microbiota has been elucidated through multidimensional modeling of both food component and macronutrient intake. However, the broad distribution of wild generalist and the intricate complexity of their food component hinder our capacity to ascertain the degree to which their gut microbiota assist in adapting to spatial dietary variations. We examined variation in patterns of the gut microbial community according to changes in diet and in a colobine monkey with a regional variable diet, the golden snub-nosed monkey (Rhinopithecus roxellana). Specifically, we analyse the interactions between variation in food component, macronutrient intake and the gut microbial community. We compared monkeys from four populations by quantifying food component and macronutrient intake, and by sequencing 16S rRNA and the microbial macro-genomes from the faecal samples of 44 individuals. We found significant differences in the diets and gut microbial compositions, in nutrient space and macronutrient intake among some populations. Variations in gut microbiota composition across distinct populations mirror the disparities in macronutrient intake, with a notable emphasis on carbohydrate. Geographical differences in the diet among of golden snub-nosed monkey populations will result in macronutrient intake variation, with corresponding differences in macronutrient intake driving regional differences in the compositions and abundances of gut microbiota. Importantly, the gut microbiota associated with core digestive functions does not vary, with the non-core gut microbiota fluctuating in response to variation in macronutrient intake. This characteristic may enable species heavily reliant on gut microbiota for digestion to adapt to diet changes. Our results further the understanding of the roles gut microbiota play in the formation of host dietary niches.

The adsorption of toxic and harmful gases through porous materials is an effective means of air pollution control. A multi-level porous carbon material with ultra-high-specific surface area was made based on rice husk biomass to improve the air pollution controlling efficiency and reduce its cost. The rice husk substrate was pretreated using T.viride spore suspension during the preparation of this material. This changes the proportion of various components in the matrix, thereby achieving an increase in the multi-level porous carbon material’s specific surface area. Its performance was analyzed through various means in the study. The results confirmed that when the activation treatment time was 60 minutes, the porous carbon material’s specific surface area was the highest, reaching 3714 m2/g. After 30 days of treatment with T.viride spore suspension, the cellulose content in rice husks decreased by about 40 g/kg. Compared to untreated porous carbon materials, after 20 days of treatment, the micropores and mesopores of these materials significantly increased. The research has successfully increased the multi-level porous carbon material’s specific surface area and achieved rapid absorption of atmospheric volatile organic compounds. The multi-level porous carbon material can enhance the air pollution controlling efficiency and reduce its cost.

Abstract The branching fraction of D + → K S 0 π 0 e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e $$ is measured for the first time using 7.93 fb −1 of e + e − annihilation data collected at the center-of-mass energy s $$ \sqrt{s} $$ = 3.773 GeV with the BESIII detector operating at the BEPCII collider, and is determined to be B D + → K S 0 π 0 e + ν e = 0.881 ± 0.017 stat . ± 0.016 syst . % $$ \mathcal{B}\left({D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e\right)=\left(0.881\pm {0.017}_{\textrm{stat}.}\pm {0.016}_{\textrm{syst}.}\right)\% $$ . Based on an analysis of the D + → K S 0 π 0 e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e $$ decay dynamics, we observe the S-wave and P-wave components with fractions of f S-wave = (6.13 ± 0.27stat. ± 0.30syst. )% and f K ¯ ∗ 892 0 = 93.88 ± 0.27 stat . ± 0.29 syst . % $$ {f}_{{\overline{K}}^{\ast }{(892)}^0}=\left(93.88\pm {0.27}_{\textrm{stat}.}\pm {0.29}_{\textrm{syst}.}\right)\% $$ , respectively. From these results, we obtain the branching fractions B D + → K S 0 π 0 S − wave e + ν e = 5.41 ± 0.35 stat . ± 0.37 syst . × 10 − 4 $$ \mathcal{B}\left({D}^{+}\to {\left({K}_S^0{\pi}^0\right)}_{S-\textrm{wave}}{e}^{+}{\nu}_e\right)=\left(5.41\pm {0.35}_{\textrm{stat}.}\pm {0.37}_{\textrm{syst}.}\right)\times {10}^{-4} $$ and B D + → K ¯ ∗ 892 0 e + ν e = 4.97 ± 0.11 stat . ± 0.12 syst . % $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}^{\ast }{(892)}^0{e}^{+}{\nu}_e\right)=\left(4.97\pm {0.11}_{\textrm{stat}.}\pm {0.12}_{\textrm{syst}.}\right)\% $$ . In addition, the hadronic form-factor ratios of D + → K ¯ ∗ 892 0 e + ν e $$ {D}^{+}\to {\overline{K}}^{\ast }{(892)}^0{e}^{+}{\nu}_e $$ at q 2 = 0, assuming a single-pole dominance parameterization, are determined to be r V = V 0 A 1 0 = 1.43 ± 0.07 stat . ± 0.03 syst . $$ {r}_V=\frac{V(0)}{A_1(0)}=1.43\pm {0.07}_{\textrm{stat}.}\pm {0.03}_{\textrm{syst}.} $$ and r 2 = A 2 0 A 1 0 = 0.72 ± 0.06 stat . ± 0.02 syst . $$ {r}_2=\frac{A_2(0)}{A_1(0)}=0.72\pm {0.06}_{\textrm{stat}.}\pm {0.02}_{\textrm{syst}.} $$ .

Abstract Short‐chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant attention due to their close association with host health. As important mediators between the gut microbiota and the host, SCFAs serve as energy substrates for intestinal epithelial cells and maintain homeostasis in host immune and energy metabolism by influencing host epigenetics, activating G protein‐coupled receptors, and inhibiting pathogenic microbial infections. This review provides a comprehensive summary of SCFAs synthesis and metabolism and offering an overview of the latest research progress on their roles in protecting gut health, enhancing energy metabolism, mitigating diseases such as cancer, obesity, and diabetes, modulating the gut‐brain axis and gut‐lung axis, and promoting bone health.

Abstract Dermatophagoides pteronyssinus (Der p) subcutaneous immunotherapy (SCIT) has demonstrated efficacy in clinical trials of childhood allergic rhinitis (AR). Currently, there is a lack of some generally accepted biomarkers that may predict the clinical response to SCIT to eventually achieve personalized therapy. In this study, 28 children with AR received Der p SCIT for 26–30 months at baseline, and four efficacy endpoints, serum interleukin (IL)-5, periostin, Der p-specific IgE (sIgE), and Der p sIgG4, were measured by ELSIA. Clinical symptoms and characteristics were assessed by questionnaires, and the associations among periostin, Der p 2 sIgE and clinical efficacy were analyzed. The results showed that SCIT demonstrated a significant reduction in Der p 1 sIgE (P

Abstract Both the pyrroloindoline core and N–CF3 moiety hold significant importance in medicinal chemistry. However, to date, no instances of constructing N–CF3-containing pyrroloindolines have been reported. Herein, we present a robust and operationally simple approach to assembling such intriguing skeletons from tryptamine-derived isocyanides through a cascade sequence, which includes an oxidative trifluorination and a subsequent halogenative cyclization. Key to the success lies in the development of a facile conversion of isocyanides to N–CF3 moiety with commercially available reagents N-halosuccinimide and Et3N·HF. The protocol features mild reaction conditions, broad functional group tolerance, good to excellent yields, and high diastereoselectivities. In addition, we demonstrate that the halide substituent within the products serves as a versatile functional handle for accessing diverse C3-quaternary-substituted N–CF3-pyrroloindolines.

Abstract Background Dysphagia, a common complication of acute stroke, is associated with increased mortality and morbidity. Acupuncture, a widely used swallowing therapy in China, has been suggested as an effective therapy for treating Post-Stroke Dysphagia (PSD) by recent meta-analyses and guidelines. The use of resting-state functional Magnetic Resonance Imaging (rs-fMRI) and Diffusion Tensor Imaging (DTI) could explore the change of regional spontaneous neural activity, functional relationships between brain regions, and white matter connectivity patterns after acupuncture intervention for PSD. This trial aims to evaluate the efficacy of acupuncture treatment for PSD and explore its central mechanism by neuroimaging. Methods/design This randomized controlled trial will recruit 40 PSD patients. All patients will be randomized to either the Real Acupuncture (RA) or Sham Acupuncture (SA) group by a ratio of 1:1. All patients will receive immediate acupuncture treatment in the MRI scanning room, followed by four weeks of long-term acupuncture treatment. The primary outcomes are the rs-fMRI and DTI indicators, which will be evaluated after the immediate and long-term acupuncture treatment. The secondary outcomes are the scales that assess the efficacy, including the Functional Oral Intake Scale (FOIS), Water Swallowing Test (WST), Swallowing Quality Of Life Questionnaire (SWAL-QOL), and National Institute of Health Stroke Scale (NIHSS). The modified version of the Massachusetts General Hospital Acupuncture Sensation Scale (M-MASS) and fMRI sensation record table will also be evaluated. Discussion This protocol presents the design of a randomized, single-blind trial that will evaluate the efficacy and explore the neural plasticity of acupuncture treatment for PSD. This trial will deepen our insight into the clinical value of acupuncture for PSD and initially probe into the time-dosage-effect mechanism of acupuncture. Trial registration numbers Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2300067480. This study was registered on 9th January 2023.

Abstract Background Acute mountain sickness (AMS) is considered the most common altitude sickness. It can be detrimental to the health of tourists who rapidly ascend high mountains, and can also impair the performance of individuals who move to the plateau for work or education. Acupuncture has been shown to improve AMS as a simple, safe, and effective nonpharmacological method, in case electro-thumbtack needle (ETN) is a more convenient form of acupuncture for both doctor and patient. There are no studies validating the effectiveness of electro-thumbtack needle in improving symptoms in participants with AMS. In this study, we will conduct a randomized controlled trial to evaluate the clinical efficacy and safety of electro-thumbtack needle in participants with AMS. Our hypothesis is that electro-thumbtack needle is safe and effective in treating participants with AMS. Methods This study is a single-center, randomized, single-blinded, and placebo-controlled study involving at least 114 participants who were diagnosed with AMS. The participants randomly assigned in a 1:1 ratio to the electro-thumbtack needle group and the sham acupuncture group. The treatment protocol involved stimulation of seven predefined acupuncture points, including Zhong Wan (RN12), bilateral Nei Guan (PC6), bilateral He Gu (LI4), and bilateral Tai Yang (EX-HN5), for approximately one minute each, with continuous application over 48 h. The primary outcome was improvement in 2018 Lake Louise score (LLS) after 48 h of treatment. Secondary outcome indicators included the incidence of participants with moderate-to-severe AMS (AMS > 5)and AMS, the LLS, visual analogue scale of headache, clinical functioning scores, the Groningen Sleep Quality Survey, the Stanford Somnolence Scale, blood pressure, oxygen saturation, and heart rate, in addition to treatment-related adverse events were also captured. Discussion This trial aims to ascertain the therapeutic benefits of ETN in mitigating AMS symptoms, thereby contributing to the evidence base for traditional medical practices, particularly acupuncture, in high-altitude medicine. Trial registration Chinese Clinical Trials Registry: ChiCTR2300073882. Registered on 24 July 2023.

Abstract Melatonin supplementation during in vitro maturation (IVM) improves porcine oocyte maturation and embryonic development by exerting antioxidative effects. Nevertheless, the mechanism by which melatonin prevents polyspermy after in vitro fertilization (IVF) remains unclear. Here, we examined the effects of melatonin on cytoplasmic maturation and the incidence of polyspermic penetration in porcine oocytes. No statistically significant difference was observed in the rate of first polar body formation between the groups (Control, Melatonin, Melatonin + Luzindole, and Melatonin + 4-P-PDOT). Interestingly, melatonin supplementation significantly improved the cytoplasmic maturation of porcine oocytes by enhancing the normal distribution of organelles (Golgi apparatus, endoplasmic reticulum and mitochondria) and upregulating organelle-related gene expressions (P

Abstract Background Pituitary adenomas (PAs) are the second most common intracranial tumor. While current diagnostic practices rely primarily on histological testing, they often fail to capture the molecular complexities of pituitary adenomas, underscoring the need for a molecular-based classification to refine therapeutic strategies and prognostic assessments. This study aims to provide a molecularly unbiased classification of pituitary adenomas and explore their unique gene expression patterns and clinical features. Methods We performed unsupervised hierarchical clustering of the gene expression profiles of 117 PA samples to identify three distinct molecular subtypes. Subsequently, we analyzed the compiled transcriptomic profiles of each individual subtype for pathway enrichment. We also validated the new classification with a validation set containing 158 PAs and 24 pituitary adenoma stem cells (PASCs). Results Consensus clustering of transcriptomic data from 117 pituitary adenoma (PA) samples identified three distinct molecular subtypes, each showing unique gene expression patterns and associated biological processes: Group I is enriched in signaling pathways, such as the cAMP signaling pathway and the calcium signaling pathway. Group II is primarily related to metabolic processes, including nitrogen metabolism and arginine biosynthesis in cancer. Group III predominantly shows enrichment in immune responses and potential malignant transformation of the disease, especially through cancer-related pathways such as the JAK–STAT signaling pathway and the PI3K–Akt signaling pathway. The immune profiling revealed distinct patterns for each subtype: Group I had higher dendritic cells and fewer CD8+ T cells, Group II had more monocytes and macrophages, and Group III had elevated levels of T cells. Additionally, there were differences in clinical characteristics and prognosis among the subtypes, with Group III having a worse prognosis, despite the smaller tumor size compared to other groups. Notably, differences in PASCs correlated with the molecular subtypes, with Group III stem cells being enriched in tumorigenesis pathways, PI3K–Akt signaling pathway and Ras signaling pathway. Conclusion Our study introduces a novel molecular classification for pituitary adenomas, independent of traditional histological methods. Each subtype features distinct genetic, molecular, and immunological profiles. We have isolated pituitary adenoma stem-like cells (PASCs), pairing them with tumor tissues for detailed transcriptomic analysis. These PASCs exhibit diverse molecular traits consistent with the new classification.

The complete mitochondrial genome of Saldoida armata (Heteroptera: Saldidae) is 16,049 bp in length, comprising 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs) and a control region. All the PCGs are initially encoded by ATN, TTG or GTG, and terminated coding with TAA or a single T. With the exception of trnS(AGN), all tRNAs exhibit a typical cloverleaf secondary structure. Phylogenetic analysis reveals the sister relationship of S. armata with other Saldidae members. The complete mitogenome of S. armata will provide useful genetic information for species identification, phylogenetic analysis and conservation of this species.

Zanthoxylum bungeanum, as a vital spice, the presence of its bitter components has a notable impact on the overall flavor of the food. To deeply explore the formation mechanism of the bitter components in Z. bungeanum and correlated influencing factors, this study used bitterness intensity as an indicator and employed sensory evaluation to optimize the processing conditions of Z. bungeanum during boiling and frying through single-factor optimization. Furthermore, organic solvent extraction, solid-phase extraction, and preparative high-performance liquid chromatography were used to isolate and concentrate the bitter fractions from Z. bungeanum water and oil. Subsequently, taste dilution analysis was employed to evaluate the contribution of these bitter fractions to the sensory characteristics of food. Additionally, high-performance liquid chromatography-mass spectrometry was adopted to identify the bitter components in Z. bungeanum water and oil. The results indicated that during the boiling process, increasing the amount of Z. bungeanum and extending the boiling time intensified the bitterness, while the bitterness of Z. bungeanum during frying process increased with raised temperature, extended frying time, and increased amount of Z. bungeanum. The recommended conditions for consumption and processing of Z. bungeanum water and Z. bungeanum oil were as follows: Z. bungeanum water was recommended to be boiled at 100 ℃ for 5 min, and the dosage of Z. bungeanum could be controlled at less than 2 g to reduce the bitter flavor. Z. bungeanum oil was recommended to be fried at 105~120 ℃ for 10~30 min, and the amount of Z. bungeanum could be added moderately to keep the bitter flavor low. The main bitter substances in Z. bungeanum water might be quercetin-3-rhamnose gentiobioside, quercetin-3,7-di-O-β-D-glucopyranoside, quercetin-3-O-robinobioside, and nuciferine, while the primary bitter compounds in Z. bungeanum oil were hydroxy-α-sanshool and hydroxy-β-sanshool. This study provides data reference and theoretical basis for the processing, quality control, and bitterness reduction of Z. bungeanum.

Heat shock proteins (HSPs), also known as heat stress proteins, can be divided into five main families, including HSP100, HSP90, HSP70, HSP60, and small heat shock proteins (sHSPs), according to their molecular weight. Further studies have shown that HSPs represent a class of highly conserved proteins that widely exist in the subcellular compartments of prokaryotic and eukaryotic cells. They have many functions, such as protein folding, repair, and immunity, and play important roles in organism growth and development. For example, Dmhsp70-A and Dmhsp70-B showed similar trends in the development of asexual embryos in Daphnia magna. However, they exhibited different trends in the development of sexual embryos despite high expression in both embryo types. Penaeus japonicus is one of the most important commercial shrimp species in China, Japan, and Southeast Asian countries. Relevant studies have shown that hsp genes widely exist in P. japonicus and play important roles in growth and development. For example, hsp10 and hsp60 were expressed in all tissues of P. japonicus, and the differential expression of hsp60 was identified in the early development stages. However, previous studies were based on single genes, and more systematic studies based on the role of the hsp gene family in the growth and development of P. japonicus have not been published. Our laboratory has completed the genome sequence of P. japonicus, which provides basic data for analyzing the molecular mechanism of hsp in the growth and development of P. japonicus. To further study the characteristics of the hsp gene family in P. japonicus and the expression characteristics of hsp genes during different development stages, the hsp gene family of P. japonicus was identified and analyzed using bioinformatics methods, and variation in its expression during the development of P. japonicus was measured using reverse transcription and quantitative real-time (RT-qPCR). Fifteen members of the hsp gene family were identified from the whole genome of P. japonicus via bioinformatics analysis, and their gene structures, motif compositions, chromosome localizations, and phylogenetic characteristics were analyzed. The expression of hsp genes in maternal-to-zygotic cells, blastocysts, gastrulae, limb buds, intramembranous nauplii, stage 1 nauplii, stage 1 zoeae, stage 1 myses, and stage 1 post-larval juveniles of P. japonicus was measured using qPCR. A total of 15 hsp genes were identified, including 1 hsp10, 2 hsp20, 2 hsp40, 1 hsp60, 6 hsp70, and 3 hsp90 genes. The physicochemical properties of seven proteins were stable, with instability coefficients less than 40. Subcellular localization results showed that most of the hsp gene family members were located in the cytoplasm, as seven hsp genes were localized to the cytoplasm, two to the nucleus, two to the extracellular region, two to the endoplasmic reticulum, and two to the mitochondria. Isoelectric point (pI) is related to the number and proportion of acidic and basic amino acids contained in a protein. Most HSPs exhibited a pI < 7, suggesting they were acidic proteins. The 15 hsp genes were located on 11 chromosomes. Phylogenetic tree analysis showed that most of the HSP family members were first clustered with HSP family members from species such as Penaeus monodon, Litopenaeus vannamei, and Fenneropenaeus chinensis and then with HSP family members of other species, which was consistent with the traditional taxonomic status. A few HSP family members were clustered first with HSP family members from Eriocheir sinensis, D. melanogaster, and other insects, and then with HSP family members from other species. Motif analysis showed that the hsp gene family was highly conserved; however, the functions of different families were quite different. Structural domain analysis showed that the HSP family included cpn10-, metazoan ACD-, DnaJ bact superfamily-, GroEL-, PTZ00009 superfamily-, dnaK-, HSP70 superfamily-, HSP90 superfamily-, PRK14083 superfamily-, and HATpase_HSP90-like domains. Each gene family contained corresponding domains and was important in molecular chaperone processes. hsp genes were expressed in different developmental stages of P. japonicus and played important roles in growth and development. The trend of Pjhsp10-19.517 was similar to that of Pjhsp60-19.518, which was highly expressed during embryonic development and significantly downregulated during larval development. This is consistent with the conclusion of previous studies that HSP60 and HSP10 are molecular chaperones for each other to ensure the correct folding of the target protein. The hsp genes such as Pjhsp40-15.349, Pjhsp70-39.287, Pjhsp70-1.298, and Pjhsp90 were highly expressed in the embryonic period; Pjhsp20, Pjhsp70-3.662, Pjhsp70-15.369, Pjhsp70-32.916, and Pjhsp90-12.759 were highly expressed during the larval period. The hsp genes expressed at high levels during the embryonic period satisfy the high protein requirements of embryos by playing the role of molecular chaperone and regulating the transcription of vitellogenin to meet the embryonic need for vitellin. The hsp genes expressed at high levels during the larval period protect the body from environmental pressure, pathogens, and xenobiotics through a synergistic immune effect. The authors believe that hsp genes play important roles in the growth and development of P. japonicus, and the specific pathways and mechanisms should be further studied. This study provides basic data for further investigations of the role of hsp genes in the growth and development of P. japonicus.

Identifying novel compound–protein interactions (CPIs) plays a pivotal role in target identification and drug discovery. Although the recent multimodal methods have achieved outstanding advances in CPI prediction, they fail to effectively learn both intra-modality and inter-modality dynamics, which limits their prediction performance. To address the limitation, we propose a novel multimodal tensor fusion CPI prediction framework, named MMTF-CPI, which contains three unimodal learning modules for structure, heterogeneous network and transcriptional profiling modalities, a tensor fusion module and a prediction module. MMTF-CPI is capable of focusing on both intra-modality and inter-modality dynamics with the tensor fusion module. We demonstrated that MMTF-CPI is superior to multiple state-of-the-art multimodal methods across seven datasets. The prediction performance of MMTF-CPI is significantly improved with the tensor fusion module compared to other fusion methods. Moreover, our case studies confirmed the practical value of MMTF-CPI in target identification. Via MMTF-CPI, we also discovered several candidate compounds for the therapy of breast cancer and non-small cell lung cancer.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

5-formylcytidine (f5C) is a unique post-transcriptional RNA modification found in mRNA and tRNA at the wobble site, playing a crucial role in mitochondrial protein synthesis and potentially contributing to the regulation of translation. Recent studies have unveiled that the f5C modifications may drive mitochondrial mRNA translation to power cancer metastasis. Accurate identification of f5C sites is essential for further unraveling their molecular functions and regulatory mechanisms, but there are currently no computational methods available for predicting their locations. In this study, we introduce an innovative ensemble approach, successfully enabling the computational recognition of Saccharomyces cerevisiae f5C. We conducted a comprehensive model selection process that involved multiple basic machine learning and deep learning algorithms such as recurrent neural networks, convolutional neural networks and Transformer-based models. Initially trained only on sequence information, these individual models achieved an AUROC ranging from 0.7104 to 0.7492. Through the integration of 32 novel domain-derived genomic features, the performance of individual models has significantly improved to an AUROC between 0.7309 and 0.8076. To further enhance accuracy and robustness, we then constructed the ensembles of these individual models with different combinations. The best performance attained by our ensemble models reached an AUROC of 0.8391. Shapley additive explanations were conducted to explain the significant contributions of genomic features, providing insights into the putative distribution of f5C across various topological regions and potentially paving the way for revealing their functional relevance within distinct genomic contexts. A freely accessible web server that allows real-time analysis of user-uploaded sites can be accessed at: www.rnamd.org/Resf5C-Pred.

AbstractContext Sepsis-induced acute lung injury (ALI) is a severe condition with limited effective therapeutics; nicotinamide mononucleotide (NMN) has been reported to exert anti-inflammatory activities.Objective This study explores the potential mechanisms by which NMN ameliorates sepsis-induced ALI in vivo and in vitro.Materials and methods Cultured MH-S cells and a murine model were used to evaluate the effect of NMN on sepsis-induced ALI. MH-S cells were stimulated with LPS (1 μg/mL) and NMN (500 μM) for 12 h grouping as control, LPS, and LPS + NMN. Cell viability, apoptotic status, and M1/2 macrophage-related markers were detected. The mice were pretreated intraperitoneally with NMN (500 mg/kg) and/or EX-527 (5 mg/kg) 1 h before LPS injection and randomized into 7 groups (n = 8): control, LPS, LPS + NMN, NMN, LPS + NMN + EX-527 (a SIRT1 inhibitor), LPS + EX-527, and EX-527. After 12 h, lung histopathology, W/D ratio, MPO activity, NAD+ and ATP levels, M1/2 macrophage-related markers, and expression of the SIRT1/NF-κB pathway were detected.Results In MH-S cells, NMN significantly decreased the apoptotic rate from 12.25% to 5.74%. In septic mice, NMN improved the typical pathologic findings in lungs and reduced W/D ratio and MPO activity, but increased NAD+ and ATP levels. Additionally, NMN suppressed M1 but promoted M2 polarization, and upregulated the expression of SIRT1, with inhibition of NF-κB-p65 acetylation and phosphorylation. Furthermore, inhibition of SIRT1 reversed the effects of NMN-induced M2 macrophage polarization.Conclusions NMN protects against sepsis-induced ALI by promoting M2 macrophage polarization via the SIRT1/NF-κB pathway, it might be an effective strategy for preventing or treating sepsis-induced ALI.

ObjectiveTo investigate the inhibitory effect and mechanism of lentinan on colitis-associated colorectal cancer (CAC) induced by azomethane (AOM)/dextran sulfate sodium salt (DSS) through the IL-6/ STAT3 pathway. MethodsC57BL/6 mice were randomly divided into a control group, a model group, a low-dose group (0.865 mg/kg lentinan), a medium-dose group (1.73 mg/kg lentinan), and a high-dose group (3.46 mg/kg lentinan). Except the control group, CAC was induced by AOM/DSS in the other groups, and corresponding drugs were injected intraperitoneally during the modeling process. Body mass, disease activity index (DAI) score, colon length, and tumor number were compared among all groups. Hematoxylin–eosin staining was used to observe the pathological morphology of colon. ELISA was utilized to detect the IL-6, IL-1β, and IL-18 contents in serum. Western blot analysis was conducted to detect the expression levels of IL-6, p-STAT3, and c-Myc in colon tissues. ResultsThe tumor number, DAI score, serum IL-6, IL-1β, and IL-18 contents and the expression levels of IL-6, p-STAT3, and c-Myc in the colon tissue of the model group were higher than those of the control group, while the body mass and colon length were lower than those of the control group (P

Abstract Background The genus Amorphophallus (Araceae) contains approximately 250 species, most of which have high ecological and economic significance. The chloroplast genome data and the comprehensive analysis of the chloroplast genome structure of Amorphophallus is limited. In this study, four chloroplast genomes of Amorphophallus were sequenced and assembled. For the first time, comparative analyses of chloroplast genomes were conducted on the 13 Amorphophallus species in conjunction with nine published sequences. Results The Amorphophallus chloroplast genomes exhibited typical quadripartite structures with lengths ranging from 164,417 to 177,076 bp. These structures consisted of a large single copy (LSC, 90,705 − 98,561 bp), a small single copy (SSC, 14,172 − 21,575 bp), and a pair of inverted repeats (IRs, 26,225 − 35,204 bp). The genomes contain 108 − 113 unique genes, including 76 − 79 protein-coding genes, 28 − 29 tRNA genes, and 4 rRNA genes. The molecular structure, gene order, content, codon usage, long repeats, and simple sequence repeats (SSRs) within Amorphophallus were generally conserved. However, several variations in intron loss and gene expansion on the IR-SSC boundary regions were found among these 13 genomes. Four mutational hotspot regions, including trnM-atpE, atpB, atpB-rbcL and ycf1 were identified. They could identify and phylogeny future species in the genus Amorphophallus. Positive selection was found for rpl36, ccsA, rpl16, rps4, rps8, rps11, rps12, rps14, clpP, rps3, ycf1, rpl20, rps2, rps18, rps19, atpA, atpF, rpl14, rpoA, rpoC1, rpoC2 and rps15 based on the analyses of Ka/Ks ratios. Phylogenetic inferences based on the complete chloroplast genomes revealed a sister relationship between Amorphophallus and Caladieae. All Amorphophallus species formed a monophyletic evolutionary clade and were divided into three groups, including CA-II, SEA, and CA-I. Amorphophallus albus, A. krausei , A. kachinensis and A. konjac were clustered into the CA-II clade, A. paeoniifolius and A. titanum were clustered into the SEA clade, A. muelleri ‘zhuyajin1’, Amorphophallus sp, A. coaetaneus, A. tonkinensis and A. yunnanensis were clustered into CA- I clade. Conclusions The genome structure and gene content of Amorphophallus chloroplast genomes are consistent across various species. In this study, the structural variation and comparative genome of chloroplast genomes of Amorphophallus were comprehensively analyzed for the first time. The results provide important genetic information for species classification, identification, molecular breeding, and evolutionary exploration of the genus Amorphophallus.

Abstract Background Myofibroblasts constitute a significant component of the tumor microenvironment (TME) and play a pivotal role in the progression of hepatocellular carcinoma (HCC). Integrin α5 (ITGA5) is a crucial regulator in myofibroblasts of malignant tumors. Therefore, the potential of ITGA5 as a novel target for the therapeutic strategy of HCC should be investigated. Methods Digital scanning and analysis of the HCC tissue microarray were performed to locate the distribution of ITGA5 and conduct the prognosis analysis. CRISPR Cas9-mediated ITGA5 knockout was performed to establish the ITGA5-KO myofibroblast cell line. Extracellular vesicles (EVs) derived from LX2 were extracted for the treatment of HCC cells. Subsequently, the sphere-forming ability and the stemness markers expression of the treated HCC cells were examined. An orthotopic HCC mouse model with fibrotic injury was constructed to test the outcomes of ITGA5-targeting therapy and its efficacy in the programmed death-ligand 1 (PD-L1) treatment. Co-immunoprecipitation/mass spectrometry and transcriptome data were integrated to delve into the mechanism. Results The tissue microarray results revealed that ITGA5 was highly enriched in the stromal myofibroblasts of HCC tissues and contributed to enhanced tumor progression and poor prognosis. Notably, ITGA5 transmission via extracellular vesicles (EVs) from myofibroblasts to HCC cells induced the acquisition of cancer stem cell-like properties. Mechanistically, ITGA5 directly bind to YES1, facilitating the activation of YES1 and its downstream pathways, thereby enhancing the stemness of HCC cells. Furthermore, the blockade of ITGA5 impeded tumor progression driven by ITGA5+ myofibroblasts and enhanced the efficacy of treatment with PD-L1 in a mouse model of HCC. Conclusions Our findings elucidated a novel mechanism by which the EV-mediated transfer of ITGA5 from myofibroblasts to tumor cells augmented HCC stemness. ITGA5-targeting therapy helped prevent the progression of HCC and improved the efficacy of PD-L1 treatment. Graphical Abstract

Abstract Changes in lung and gut microbial communities have been associated with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate correlations between microbial changes in the lung and gut and host physiological indices in an IPF model, exploring potential mechanisms of the lung-gut axis in IPF pathogenesis. IPF model rats were established via trans-tracheal injection of bleomycin, with assessments of hematological indices, serum cytokines, lung histopathology, and microbiome alterations. Significant differences in microbial structure and composition were observed in the IPF model compared to controls, with 14 lung and 7 gut microbial genera showing significant abundance changes. Further analysis revealed 20 significant correlations between pulmonary and gut genera. Notably, 11 pairs of correlated genera were linked to the same IPF-related physiological indices, such as hydroxyproline, mean corpuscular volume (MCV), and red cell distribution width-standard deviation (RDW-SD). We identified 24 instances where a lung and a gut genus were each associated with the same physiological index, forming "lung genus—index—gut genus" relationships. Mediation analysis showed that indices like hydroxyproline, MCV, and RDW-SD mediated correlations between 10 lung genera (e.g., Cetobacterium, Clostridium XVIII ) and the gut genus Allobaculum. This study first describes gut-lung microbial interactions in pulmonary fibrosis. Mediation analysis suggests pathways underlying "lung genus—host index—gut genus" and "gut genus—host index—lung genus" correlations, thus providing clues to further elucidate the mechanisms of the “gut-lung axis” in IPF pathogenesis.

Abstract The 1957 H2N2 influenza pandemic virus [A(H2N2)pdm1957] has disappeared from humans since 1968, while H2N2 avian influenza viruses (AIVs) are still circulating in birds. It is necessary to reveal the recurrence risk and potential cross-species infection of these AIVs from avian to mammals. We find that H2 AIVs circulating in domestic poultry in China have genetic and antigenic differences compared to the A(H2N2)pdm1957. One H2N2 AIV has a dual receptor-binding property similar to that of the A(H2N2)pdm1957. Molecular and structural studies reveal that the N144S, and N144E or R137M substitutions in hemagglutinin (HA) enable H2N2 avian or human viruses to bind or preferentially bind human-type receptor. The H2N2 AIV rapidly adapts to mice (female) and acquires mammalian-adapted mutations that facilitated transmission in guinea pigs and ferrets (female). These findings on the receptor-binding, infectivity, transmission, and mammalian-adaptation characteristics of H2N2 AIVs provide a reference for early-warning and prevention for this subtype.

Abstract Background Accurately predicting hospital discharge events could help improve patient flow and the efficiency of healthcare delivery. However, using machine learning and diverse electronic health record (EHR) data for this task remains incompletely explored. Methods We used EHR data from February-2017 to January-2020 from Oxfordshire, UK to predict hospital discharges in the next 24 h. We fitted separate extreme gradient boosting models for elective and emergency admissions, trained on the first two years of data and tested on the final year of data. We examined individual-level and hospital-level model performance and evaluated the impact of training data size and recency, prediction time, and performance in subgroups. Results Our models achieve AUROCs of 0.87 and 0.86, AUPRCs of 0.66 and 0.64, and F1 scores of 0.61 and 0.59 for elective and emergency admissions, respectively. These models outperform a logistic regression model using the same features and are substantially better than a baseline logistic regression model with more limited features. Notably, the relative performance increase from adding additional features is greater than the increase from using a sophisticated model. Aggregating individual probabilities, daily total discharge estimates are accurate with mean absolute errors of 8.9% (elective) and 4.9% (emergency). The most informative predictors include antibiotic prescriptions, medications, and hospital capacity factors. Performance remains robust across patient subgroups and different training strategies, but is lower in patients with longer admissions and those who died in hospital. Conclusions Our findings highlight the potential of machine learning in optimising hospital patient flow and facilitating patient care and recovery.

Top-down environmental policies aim to mitigate environmental risks but inevitably lead to economic losses due to the market entry or exit of enterprises. This study developed a universal dynamic agent-based supply chain model to achieve tradeoffs between environmental risk reduction and economic sustainability. The model was used to conduct high-resolution daily simulations of the dynamic shifts in enterprise operations and their cascading effects on supply chain networks. It includes production, consumption, and transportation agents, attributing economic features to supply chain components and capturing their interactions. It also accounts for adaptive responses to daily external shocks and replicates realistic firm behaviors. By coupling high spatial–temporal resolution firm-level data from 18 916 chemical enterprises, this study investigates the economic and environmental impacts of an environmental policy resulting in the closure of 1800 chemical enterprises over three years. The results revealed a significant economic loss of 25.8 billion USD, ranging from 23.8 billion to 31.8 billion USD. Notably, over 80% of this loss was attributed to supply chain propagation. Counterfactual analyses indicated that implementing a staggered shutdown strategy prevented 18.8% of supply chain losses, highlighting the importance of a gradual policy implementation to prevent abrupt supply chain disruptions. Furthermore, the study highlights the effectiveness of a multi-objective policy design in reducing economic losses (about 29%) and environmental risks (about 40%), substantially enhancing the efficiency of the environmental policy. The high-resolution simulations provide valuable insights for policy designers to formulate strategies with staggered implementation and multiple objectives to mitigate supply chain losses and environmental risks and ensure a sustainable future.

In response to the current challenges of low cutting efficiency and poor surface quality in processing single-crystal silicon, this article proposes the utilization of the micro-discharge abrasive cutting (MDAC) method for processing single-crystal silicon. A comprehensive comparison is conducted among the processing characteristics of the new cutting method and fixed abrasive wire sawing (FAWS) and wire electrical discharge machining (WEDM), including cutting efficiency, surface morphology, subsurface damage, surface roughness, wire saw wear, elemental spectrum analysis, and kerf width. Besides, two material removal modes at different feed rates are discussed. The results indicate that compared with WEDM, MDAC has the advantages of minimal subsurface damage, low surface roughness, low residual elements, and small kerf width. MDAC has higher cutting efficiency and shallower scratch depth than FAWS. However, compared with WEDM and FAWS, MDAC results in more significant wire saw wear and leaves a small amount of residual nickel on the silicon surface. In MDAC, the discharge occurs first. When the discharge energy within the pulse width is sufficient to remove the material within the current pulse cycle, the material is completely removed by the discharge action, the discharge products remain on the surface of the silicon wafer. When the discharge energy is insufficient to remove the material within the current pulse cycle, the silicon ingot is removed under the combined action of discharge and grinding, the diamond on wire saw surface will remove most of the discharge products.

Abstract Background The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma (HCC) remains poor. Although serine‐ and arginine‐rich splicing factor (SRSF) family members play crucial roles in tumors, their impact on tumor immunology remains unclear. This study aimed to elucidate the role of SRSF10 in HCC immunotherapy. Methods To identify the key genes associated with immunotherapy resistance, we conducted single‐nuclear RNA sequencing, multiplex immunofluorescence, and The Cancer Genome Atlas and Gene Expression Omnibus database analyses. We investigated the biological functions of SRSF10 in immune evasion using in vitro co‐culture systems, flow cytometry, various tumor‐bearing mouse models, and patient‐derived organotypic tumor spheroids. Results SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8+ T cell activity. Mechanistically, SRSF10 interacted with the 3′‐untranslated region of MYB, enhancing MYB RNA stability, and subsequently upregulating key glycolysis‐related enzymes including glucose transporter 1 (GLUT1), hexokinase 1 (HK1), lactate dehydrogenase A (LDHA), resulting in elevated intracellular and extracellular lactate levels. Lactate accumulation induced histone lactylation, which further upregulated SRSF10 expression. Additionally, lactate produced by tumors induced lactylation of the histone H3K18la site upon transport into macrophages, thereby activating transcription and enhancing pro‐tumor macrophage activity. M2 macrophages, in turn, inhibited the enrichment of CD8+ T cells and the proportion of interferon‐γ+CD8+ T cells in the tumor microenvironment (TME), thus creating an immunosuppressive TME. Clinically, SRSF10 could serve as a biomarker for assessing immunotherapy resistance in various solid tumors. Pharmacological targeting of SRSF10 with a selective inhibitor 1C8 enhanced the efficacy of programmed cell death 1 (PD‐1) monoclonal antibodies (mAbs) in both murine and human preclinical models. Conclusions The SRSF10/MYB/glycolysis/lactate axis is critical for triggering immune evasion and anti‐PD‐1 resistance. Inhibiting SRSF10 by 1C8 may overcome anti‐PD‐1 tolerance in HCC.